9R1X | pdb_00009r1x

PLK1 SURFACE ENTROPY REDUCTION (SER) MUTANT IN COMPLEX WITH INHIBITOR BI 2536

PDB DOI: https://doi.org/10.2210/pdb9R1X/pdb

Classification: TRANSFERASE
Organism(s): Homo sapiens
Expression System: Trichoplusia ni
Mutation(s): Yes

Deposited: 2025-04-28 Released: 2025-11-26
Deposition Author(s): Hillig, R.C., Schulze, V.K., Siemeister, G., Schmitz, A.A., Eberspaecher, U.
Funding Organization(s): Not funded

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.84 Å
R-Value Free:
0.277 (Depositor), 0.278 (DCC)
R-Value Work:
0.219 (Depositor), 0.220 (DCC)
R-Value Observed:
0.222 (Depositor)

Starting Model: experimental
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wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.1 of the entry. See complete history.

Literature

Polo-like kinase 1-inhibitor co-complex structures via the surface-entropy reduction approach and a DARPin-assisted approach.

Eberspaecher, U., Schmitz, A.A., Siemeister, G., Bomer, U., Bandeiras, T.M., Matias, P.M., Schulze, V.K., Hillig, R.C.

(2025) Acta Crystallogr D Struct Biol 81: 718-733

PubMed: 41246821 Search on PubMed
DOI: https://doi.org/10.1107/S2059798325009325
Primary Citation of Related Structures:
9R1W, 9R1X, 9R1Y, 9R8B, 9R8C

PubMed Abstract:
Polo-like kinase 1 (PLK1) is a major regulator of cell division and has been pursued as a drug target for cancer therapy for a long time. Crystallization of the kinase domain has proven to be exceptionally challenging. Previously, we published a crystallization approach using a PLK1-specific designed ankyrin-repeat protein (DARPin) as a crystallization facilitator. Here, we report an alternative route: crystallization was successful after the introduction of a double mutation which reduced surface entropy and enabled the formation of a new crystal contact. This new PLK1 crystallization system was used to determine the first co-complex crystal structure of the Bayer thiazolidinone lead series, as well as crystal structures with representatives of two competitor inhibitor series. The molecular binding modes of these three inhibitors are analysed and discussed, and the surface-entropy reduction approach is compared with the surface modifications employed by us and others to enable the crystallization of PLK1.

Organizational Affiliation

Research and Development, Pharmaceuticals, Bayer AG, Muellerstrasse 178, 13353 Berlin, Germany.

Macromolecule Content

Total Structure Weight: 74.9 kDa
Atom Count: 4,975
Modeled Residue Count: 584
Deposited Residue Count: 650
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Serine/threonine-protein kinase PLK1	A, B	325	Homo sapiens	Mutation(s): 2 Gene Names: PLK1, PLK EC: 2.7.11.21
UniProt & NIH Common Fund Data Resources
Find proteins for P53350 (Homo sapiens) Explore P53350 Go to UniProtKB: P53350
PHAROS: P53350 GTEx: ENSG00000166851
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P53350
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 3 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
R78 (Subject of Investigation/LOI) Query on R78 Download Ideal Coordinates CCD File SDF format, chain C [auth A] SDF format, chain H [auth B] MOL2 format, chain C [auth A] MOL2 format, chain H [auth B] mmCIF format, chain C [auth A] mmCIF format, chain H [auth B]	C [auth A], H [auth B]	4-{[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-5,6,7,8-tetrahydropteridin-2-yl]amino}-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide C₂₈ H₃₉ N₇ O₃ XQVVPGYIWAGRNI-JOCHJYFZSA-N		Interactions Focus chain C [auth A] Focus chain H [auth B] Interactions & Density Focus chain C [auth A] Focus chain H [auth B]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain I [auth B] SDF format, chain J [auth B] SDF format, chain L [auth B] SDF format, chain G [auth A] SDF format, chain E [auth A] SDF format, chain D [auth A] MOL2 format, chain F [auth A] MOL2 format, chain I [auth B] MOL2 format, chain J [auth B] MOL2 format, chain L [auth B] MOL2 format, chain G [auth A] MOL2 format, chain E [auth A] MOL2 format, chain D [auth A] mmCIF format, chain F [auth A] mmCIF format, chain I [auth B] mmCIF format, chain J [auth B] mmCIF format, chain L [auth B] mmCIF format, chain G [auth A] mmCIF format, chain E [auth A] mmCIF format, chain D [auth A]	D [auth A] E [auth A] F [auth A] G [auth A] I [auth B] D [auth A], E [auth A], F [auth A], G [auth A], I [auth B], J [auth B], L [auth B]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain D [auth A] Focus chain E [auth A] Focus chain F [auth A] Focus chain G [auth A] Focus chain I [auth B] Focus chain J [auth B] Focus chain L [auth B] Interactions & Density Focus chain D [auth A] Focus chain E [auth A] Focus chain F [auth A] Focus chain G [auth A] Focus chain I [auth B] Focus chain J [auth B] Focus chain L [auth B]
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain K [auth B] MOL2 format, chain K [auth B] mmCIF format, chain K [auth B]	K [auth B]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain K [auth B] Interactions & Density Focus chain K [auth B]